Cyclin-Dependent Kinase 4 is expected to be a therapeutic target for hepatocellular carcinoma metastasis using integrated bioinformatic analysis

Abstract

ABSTRACT Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide. HCC cells possess biological characteristics of high invasion and metastasis. In this respect, to prevent cancer cell invasion and metastasis and early active intervention, we herein screened through the TCGA database for further prognostic analysis including overall survival and disease-free survival . The Kaplan-Meier curve suggested that Cyclin-Dependent Kinase 4 (CDK4) might be an independent prognostic factor for HCC. Moreover, we performed mRNA expression analysis to measure CDK4 levels in normal liver tissues and HCC tissues, and immunohistochemistry analysis to detect protein level of CDK4 in Non-tumor tissue and HCC tissues . Our findings indicated that the expression of CDK4 was significantly higher in tumor tissues compared with Non-tumor tissue in HCC, which increased from HCC stage 1 to 3. Furthermore, the results of transwell-assay indicated that knocking down CDK4 significantly suppresses the invasion and migration of HCC cells, and the results of bioinformatics analysis revealed that genes closely associated with CDK4 are potentially worthy of further investigation. Additionally, the results of Western Blot indicated CDK4 regulates epithelial mesenchymal transition in HCC,and CDK4 appears to regulate EMT and HCC progression via the Wnt/β-catenin pathway. Collectively, this study found the key target gene through bioinformatic analysis and further functional validation through cell experiments. In particular, CDK4 is anticipated to become a crucial hub gene to snipe the metastasis of cancer cells in HCC. Abbreviations: Hepatocellular carcinoma (HCC);Cyclin-Dependent Kinase 4(CDK4);Genomic Data Commons (GDC); genes; EC, Endometrial cancer; GEO, gene expression omnibus; GO, Gene Ontology; GSEA, Gene set enrichment analysis; KEGG, Database; TCGA, The Cancer Genome Atlas; TSGs, tumor suppressor genes;epithelial mesenchymal transition (EMT).